Shen Zhijie, Zeng Lixiong, Zhang Zhihui
Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan, China.
Mol Ther Nucleic Acids. 2020 Oct 22;22:1016-1024. doi: 10.1016/j.omtn.2020.10.019. eCollection 2020 Dec 4.
Adult cardiac hypoxia as a crucial pathogenesis factor can induce detrimental effects on cardiac injury and dysfunction. The global transcriptome and translatome reflecting the cellular response to hypoxia have not yet been extensively studied in myocardium. In this study, we conducted RNA sequencing (RNA-seq) and ribosome profiling technique (polyribo-seq) in rat heart tissues and H9C2 cells exposed to different periods of hypoxia stress and . The temporal gene-expression profiling displayed the distinction of transcriptome and translatome, which were mainly concentrated in cell apoptosis, autophagy, DNA repair, angiogenesis, vascular process, and cardiac cell proliferation and differentiation. A large number of genes such as GNAI3, SEPT4, FANCL, BNIP3, TBX3, ESR2, PTGS2, KLF4, and ADRB2, whose transcript and translation levels are closely correlated, were identified to own a common RNA motif "5'-GAAGCUGCC-3'" in 5' UTR. NCBP3 was further determined to recognize this RNA motif and facilitate translational process in myocardium under hypoxia stress. Taken together, our data show the close connection between alterations of transcriptome and translatome after hypoxia exposure, emphasizing the significance of translational regulation in related studies. The profiled molecular responses in current study may be valuable resources for advanced understanding of the mechanisms underlying hypoxia-induced effect on heart diseases.
成人心脏缺氧作为一个关键的发病机制因素,可对心脏损伤和功能障碍产生有害影响。反映细胞对缺氧反应的全转录组和翻译组在心肌中尚未得到广泛研究。在本研究中,我们对暴露于不同时间段缺氧应激的大鼠心脏组织和H9C2细胞进行了RNA测序(RNA-seq)和核糖体分析技术(多核糖体-seq)。时间基因表达谱显示了转录组和翻译组的差异,主要集中在细胞凋亡、自噬、DNA修复、血管生成、血管过程以及心脏细胞增殖和分化方面。大量转录本和翻译水平密切相关的基因,如GNAI3、SEPT4、FANCL、BNIP3、TBX3、ESR2、PTGS2、KLF4和ADRB2,被发现在5'UTR中拥有一个共同的RNA基序“5'-GAAGCUGCC-3'”。进一步确定NCBP3可识别该RNA基序并促进缺氧应激下心肌中的翻译过程。综上所述,我们的数据表明缺氧暴露后转录组和翻译组变化之间存在密切联系,强调了翻译调控在相关研究中的重要性。本研究中分析的分子反应可能是深入了解缺氧诱导心脏病作用机制的宝贵资源。